Healthy Subjects
Conditions
Keywords
Quizartinib
Brief summary
This study will evaluate the effect of CYP3A weak inducer rufinamide on the pharmacokinetics (PK) of Quizartinib in healthy subjects
Detailed description
This is a clinical pharmacology study with 2 treatment groups (Test treatment group receiving both rufinamide weak CYP3A inducer and quizartinib and Reference treatment group receiving quizartinib only) investigating the effect of rufinamide on the PK of quizartinib in healthy subjects.
Interventions
DRUGQuizartinib
Single oral dose of 60 mg
DRUGRufinamide
Twice daily (BID) dose of 400 mg on Days 1 through 32
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
No masking.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Male and female subjects 18 to 55 years of age (inclusive), with a BMI of 18 kg/m2 to 32 kg/m2 (inclusive) at Screening. * Has vital signs (measured after subject has been supine for at least 5 minutes) at Screening within the following ranges: heart rate: 50-100 beats per minute (bpm); systolic blood pressure (BP): 90-145 mmHg; diastolic BP: 50-95 mmHg. Out-of-range vital signs may be repeated once. * Liver function test results (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], and total bilirubin \[TBbil\]) must be equal to or below the upper limit of normal (ULN). Hemoglobin levels must be ≥11.5 g/dL for female subjects and ≥12.5 g/dL for male subjects. * In females, documented surgical sterilization (i.e., documented hysterectomy, bilateral tubal ligation, or bilateral salpingo-oophorectomy, Essure® with hysterosalpingogram \[documentation to confirm tubal occlusion 12 weeks after procedure\]), postmenopausal status for at least 1 year (follicle stimulating hormone \[FSH\] \> 40 mIU/mL serum and estradiol \<40 pg/mL \[\<147 pmol/L\] at Screening), or agreement to have sterile male partner, or agreement to use 1 of the protocol-approved means of contraception from Screening until 7 months after the dose of quizartinib. * In males, documented surgical sterilization, or sexual abstinence, or agreement to use 1 of the protocol-approved means of contraception from Screening until 4 months after the dose of quizartini Key
Exclusion criteria
* Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormality) that could interfere with subject's safety, obtaining informed consent, compliance to the study procedures, or the validity of the study results. * History of a clinically significant illness, in the opinion of the Investigator, within 4 weeks prior to administration of quizartinib. * History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically significant and/or a QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 milliseconds (ms) at Screening. * Females who are pregnant or breastfeeding * Laboratory results (serum chemistry, hematology, and urinalysis) outside the normal range, if considered clinically significant by the investigator. Estimated creatinine clearance (CrCl)\<90 mL/min (calculated by using the Cockcroft-Gault Equation) at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter: Cmax | From day of first dose, Day 1, up to Day 33 | Cmax is defined as maximum concentration, determined directly from individual concentration-time data |
| Pharmacokinetic Parameter: AUClast | From day of first dose, Day 1, up to Day 33 | AUClast is defined as area under the concentration-time curve from time-zero to the time of the last quantifiable concentration; calculated using the linear up log down |
| Pharmacokinetic Parameter: AUCinf | From day of first dose, Day 1, up to Day 33 | AUCinf is defined as area under the concentration-time curve from time-zero extrapolated to infinity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent Adverse Events (TEAEs) | From day of first dose, Day 1 up to the last day of Safety Follow-up, up to approximately 40 days | TEAEs are defined as new AEs that occur after the first dose of study drug |
Countries
United States
Outcome results
None listed